Dyskinesia in Parkinson's Disease (Study P04501)

Off time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the off state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the off state.

Time frame: Baseline (Week -1) and up to 12 weeks

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the off state) was used for analysis.

Dyskinesias refers to maintenance therapy side effects of chorea, dystonia, or in combination (that occur in the ON time). Hours spent with dyskinesias (troublesome and not troublesome) were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A negative change from baseline signifies less time spent with dyskinesia.

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the on state with troublesome and not troblesome dyskinesias) for the assessment week was used for analysis.

Off time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). Hours spent in the off state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with treatment effect and baseline covariate. A negative change from baseline signifies less time spent in the off state.

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the off state) for the assessment week was used for analysis.

On time refers to periods of adequate control of Parkinson disease symptoms (symptoms better or absent). Hours spent in the on state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. A positive (+) change from baseline signifies more time spent in the on state.

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the on state) for the assessment week was used for analysis.

On time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Dyskinesias refers to maintenance therapy (e.g., L-dopa) side effects of chorea, dystonia, or in combination. Hours spent in the on state with no dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained from an ANCOVA model with effect for treatment & baseline covariate. A (+) change from baseline signifies more time spent in the on state (no dyskinesias).

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the on state with no dyskinesias) for the assessment week was used for analysis.

On time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Troublesome dyskinesias refers to maint. therapy side effects of chorea, dystonia, or in combination that impair function. Hours spent in the on state without troubles. dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A (+) change from baseline signifies more time spent in the on state (without troubles. dyskinesias).

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the on state without troublesome dyskinesias) for the assessment week was used for analysis.

On time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Troublesome dyskinesias refers to maintenance therapy side effects of chorea, dystonia, or in combination that impair function. Hours spent in the on state with troublesome dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A (+) change from baseline signifies more time spent in the on state (troublesome dyskinesias).

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the on state with troublesome dyskinesias) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 10) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 10 would be reported as BL \>2 to WK10 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 10

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 12) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 12 would be reported as BL \>2 to WK12 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 2) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 2 would be reported as BL \>2 to WK2 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 2

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 4) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 4 would be reported as BL \>2 to WK4 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 4

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 6) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 6 would be reported as BL \>2 to WK6 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 6

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 8) (as reported by the participant). For example, someone who had \>2 sleep attacks at BL who had a decrease of 1-2 by Week 8 would be reported as BL \>2 to WK8 1-2. BL = baseline. WK = week.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Week 8

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Hours spent in the sleep state were recorded using a daily diary at least 3 full days before scheduled visit. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A positive change from baseline means more time asleep and a negative change means less time asleep.

Time frame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (total sleep time) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. Part 1 assesses mentation (4 items scored from 0 \[best\] to 4 \[worst\]; total range 0-16). Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 1) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. Part 2 assesses daily living (13 items scored from 0 \[best\] to 4 \[worst\]; total range 0-52). Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 2) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 3 subscale assesses motor function across 14 categories for 27 items. Scores for each item range from 0 (best) to 4 (worst) with a total range of 0-108. Assessments were obtained at baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Time frame: Baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 3) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 3 subscale assesses motor function across 14 categories for 27 items. Scores for each item range from 0 (best) to 4 (worst) with a total range of 0-108. Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled standard deviation were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 3) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 4 subscale assesses complications of therapy over the past week for a total of eleven question items. The first three questions and question 8 are rated from 0 (best) to 4 (worst), and the remaining seven questions are simple no (0) / yes (1) questions. The total subscale score ranges from 0 to 23. Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Time frame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline date (UPDRS Part 4) for the assessment week was used for analysis.